title: Metabolic and bioprocess engineering for production of selenized yeast with increased content of seleno-methylselenocysteine.
abstract: Specific Se-metabolites have been recognized to be the main elements responsible for beneficial effects of Se-enriched diet, and Se-methylselenocysteine (SeMCys) is thought to be among the most effective ones. Here we show that an engineered Saccharomyces cerevisiae strain, expressing a codon optimized heterologous selenocysteine methyltransferase and endowed with high intracellular levels of S-adenosyl-methionine, was able to accumulate SeMCys at levels higher than commercial selenized yeasts. A fine tuned carbon- and sulfate-limited fed-batch bioprocess was crucial to achieve good yields of biomass and SeMCys. Through the coupling of metabolic and bioprocess engineering we achieved a ∼24-fold increase in SeMCys, compared to certified reference material of selenized yeast. In addition, we investigated the interplay between sulfur and selenium metabolism and the possibility that redox imbalance occurred along with intracellular accumulation of Se. Collectively, our data show how the combination of metabolic and bioprocess engineering can be used for the production of selenized yeast enriched with beneficial Se-metabolites.
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden. valeria.mapelli@chalmers.se
authors.forename: Valeria
authors.initials: V
authors.lastname: Mapelli
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hillestrøm
authors.forename: Emese
authors.initials: E
authors.lastname: Kápolna
authors.forename: Erik H
authors.initials: EH
authors.lastname: Larsen
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Olsson
mesh_terms: D027883:Astragalus Plant / Q000201:enzymology / Q000235:genetics; D003545:Cysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods*; D008780:Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D016566:Organoselenium Compounds; D014674:Plant Proteins, Dietary / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D017279:Selenocysteine / Q000031:analogs & derivatives
chemical_list: D016566:Organoselenium Compounds; D014674:Plant Proteins, Dietary; D011994:Recombinant Proteins; D017279:Selenocysteine; D008780:Methyltransferases; C100751:selenocysteine methyltransferase; D003545:Cysteine; C002979:selenomethylselenocysteine